This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. COP9 Signalosome (CSN) plays a critical role in regulating the activity of cullin-RING ubiquitin ligases (CRLs). CSN works by cleaving the ubiquitin-like protein Nedd8 from the cullin subunit of CRLs. We seek to understand how CSN works, and how its activity is controlled. One of our strategies to address these questions is to affinity-purify CSN from different sources including yeast and human cells, and evaluate by multidimensional mass spectrometry the polypeptides that co-precipitate with CSN.